Human epidermal growth factor (EGF) module-containing mucin-like hormone receptor 3 is a new member of the EGF-TM7 family that recognizes a ligand onhuman macrophages and activated neutrophils

The epidermal growth factor (EGF)-TM7 subgroup of G-protein-coupled recepto rs is composed predominantly of leukocyte-restricted glycoproteins defined by their unique hybrid structure, in which extracellular EGF-like domains a re coupled to a seven-span transmembrane moiety via a mucin-like stalk. The EGF-TM7 group comprises mouse F4/80, human EGF module-containing mucin-lik e hormone receptor (EMR) 1, human EMR2, and human and mouse CD97, the genes for which map to human chromosome 19p13 and the syntenic regions of the mo use genome. In this study we describe the cloning and characterization of E MR3, a novel human EGF-TM7 molecule, and show the existence of its cellular ligand. The EMR3 gene maps closely to the existing members of the EGF-TM7 family on human chromosome 19p13.1 and, in common with other EGF-TM7 genes, is capable of generating different protein isoforms through alternative sp licing. Two alternative splice forms have been isolated: one encoding a 652 -amino acid cell surface protein consisting of two EGF-like domains, a muci n stalk, and a putative G-protein-coupled receptor domain and the other enc oding a truncated soluble form containing only two EGF-like domains. As wit h other members of the EGF-TM7 family, EMR3 mRNA displays a predominantly l eukocyte-restricted expression pattern, with highest levels in neutrophils, monocytes, and macrophages, Through the use of soluble EMR3 multivalent pr obes we have shown the presence of a ligand at the surface of monocyte-deri ved macrophages and activated human neutrophils. These interactions suggest a potential role for EMR3 in myeloid-myeloid interactions during immune an d inflammatory responses.